1. Field of the invention
The present invention relates to a spectroscopic method for measuring the concentration changes of sugar and its derivatives in body liquids, for example in blood, using a non-invasive technique which does not require taking a sugar medium as a sample from the body for examination, and more particularly to a method and apparatus for detecting the polarization ratio of native emission of luminescence centers in a visible and/or near infrared region of spectrum from body liquid chromophores undergoing interaction with an optically active medium such as sugar.
2. Related art
The current state of the art in measuring sugar levels in body liquids or other objects such as foods, fruits and other agricultural products requires taking a sample from the object during the examination process. Special instruments are available for the purpose of determining blood glucose levels in people with diabetes. The technology uses a small blood sample obtained from a finger prick which is placed on chemically prepared strips and inserted into a portable instrument. The instrument analyzes the blood sample and provides a blood glucose level measurement. Diabetics must prick their fingers, sometimes up to four times a day, to draw blood for monitoring their glucose levels.
To eliminate the pain of drawing blood, as well as to eliminate a source of potential infection, non-invasive optical methods for sugar determination were invented and use absorption, transmission or reflection methods for spectroscopically analyzing blood glucose concentration.
In U.S. Pat. Nos. 3,958,560 and U.S. Pat. No. 4,014,321 to W. F. March, a unique glucose sensor to determine the glucose level in patients is described. The patient's eye is automatically scanned using a dual source of polarized radiation, each transmitting in different wavelengths at one side of the cornea of the patient. A sensor located at the other side of the cornea detects the optical rotation of the radiation that passed through the cornea. Because the level of glucose in the bloodstream of the patient is a function (not a simple one) of the glucose level in the cornea, rotation of polarization can determine the level of glucose concentration.
In U.S. Pat. No. 3,963,019 to R. S. Quandt there is described a method and apparatus for detecting changes in body chemistry, for example, glycemia, in which a beam of light is projected into and through the aqueous humor of the patient's eye. An analyzer positioned to detect the beam on its exit from the patient's eye compares the effect the aqueous humor has on said beam against a norm. The change in the glucose concentration is indicated and detected.
In U.S. Pat. No. 4,750,830 to A. St. J. Lee there is described a method of measuring the optical power of the living subject's eye and comparing it with a calibration value that corresponds to a reference blood glucose level. Optical power of the eye increases with blood glucose levels.
In U.S. Pat. No. 4,805,623 to F. Jobsis there is described a spectrophotometric method of qualitatively determining the concentration of a dilute component with a reference component of known concentration by a series of contemporaneous radiation-directing and measurements steps of radiation of selected varying wavelengths.
In U.S. Pat. No. 4,882,492 to K. J. Schlager there is described a non-invasive apparatus and related method for measuring the concentration of glucose or other blood analytes. It utilizes both diffuse reflected and transmissive infrared absorption measurements. The apparatus and method utilize non-dispersive correlation spectrometry. Differencing the light intensity between the two lights paths, one with a negative correlation filter and the other without, the apparatus provides a measure proportional to analyte concentration.
In U.S. Pat. No. 4,883,953 to K. Koashi and H. Yokota there is disclosed a method for measuring the concentration of sugar in liquids by use of near infrared light. The concentration of the sugar in the sample is determined by computing the absorption spectrum of the sugar at a different depth in the sample measured by a relatively weak power of infrared light, penetrating close to the surface in a sample, and a relatively strong power of infrared light penetrating relatively deeply in the sample.
In U.S. Pat. No. 5,009,230 to D. P. Hutchinson there is disclosed a device for the non-invasive determination of blood glucose in a patient. This glucose monitor is based upon the effect of glucose in rotating polarized infrared light. More specifically, two orthogonal and equally polarized states of infrared light of minimal absorption are passed through a tissue containing blood, and an accurate determination of change in signal intensity is made due to the angle of rotation of these states. This rotation depends upon the glucose level. This method uses transmission of infrared light through the tissue at minimum absorption of the tissue.
In U.S. Pat. Nos. 5,028,787 and 5,068,536 to R. D. Rosenthal at al. there is disclosed a near-infrared quantitative analysis instrument and method of calibration for non-invasive measures of blood glucose by analyzing near-infrared energy following interactance with venous or arterial blood, or transmission through a blood contained in a body part.
In U.S. Pat. No. 5,054,487 to R. H. Clarke there is disclosed a methods for non-invasive material analysis, in which a material is illuminated at a plurality of discrete wavelengths. Measurements of the intensity of reflected light at such wavelengths are taken, and an analysis of reflection ratios for various wavelengths are correlated with specific material properties such as concentration of analytes.
Other patents for non-invasively analyzing glucose levels in blood based on different spectroscopic, electrochemical and acoustic velocity measurement methods are as follows:
In U.S. Pat. Nos. 4,875,486 and 5,072,732 to U. Rapoport at al. there is disclosed a nuclear magnetic resonance apparatus, where predetermined water and glucose peaks are compared with the measured water and glucose peaks for determining the measured concentration.
In U.S. Pat. No. 5,056,521 to J. S. Parsons at al. there is disclosed a method in which a sample of specially collected oral fluid is placed into a monitoring instrument which generates an electrical glucose representative readout for oral fluid or whole blood.
In U.S. Pat. No. 5,119,819 to G. H. Thomas at al. there is disclosed acoustic velocity measurements for monitoring the effect of glucose concentration upon the density and adiabatic compressibility of serum.
In U.S. Pat. No. 5,139,023 to T. H. Stanley at al. there is disclosed a method for non-invasive blood glucose monitoring by correlating the amount of glucose which permeates an epithelial membrane, such as skin, with a glucose receiving medium over a specified time period. The glucose receiving medium is then removed and analyzed for the presence of glucose using conventional analytical technique.
In U.S. Pat. No. 5,140,985 to J. M. Schroeder at al. there is disclosed a measuring instrument and indicating device which gives an indication of blood glucose by metering the glucose content in sweat, or other body fluids, using a plurality of oxygen sensors covered by a semi-porous membrane. The device can be directly attached to the arm and the measuring device will react with localized sweating and indicate the wearer's blood glucose level.
The above described state of the art in non-invasive blood glucose measurements devices contains many approaches and indicates the importance of the problem. But none of the described devices have yet been marketed. Some inventors claim that instruments which are being developed give accurate blood glucose level readings and can be used for home testing by diabetics. They have limitations stemming from the use of near infrared light for measurement of absorption, transmission or reflectance; in this region of spectrum one can observe interference in absorption from other chemical components. Analyses based on only one or two wavelengths can be inaccurate if there is alcohol in the blood or any other substances that absorb at the same frequencies. In addition, these analyses can be thrown off by instrument errors, outlier samples (samples with spectra that differ from the calibration set) physiological differences between people (skin pigmentation, thickness of the finger). Methods of near infrared spectroscopy must be coupled with sophisticated mathematical and statistical techniques to distinguish between nonglucose sources and to extract a faint glucose spectral signature. Another limitation of these types of blood glucose testers is that they have to be custom calibrated for each user. The need for individual calibration results from the different combination of water levels, fat levels and protein levels in various people which cause changes in the absorption of near infrared light. Since the amount of glucose in the body is less than one thousandth that of other chemicals (and all of them possess absorption in the near infrared), variations of these constituents which exist among people may make universal calibration unlikely.
Other, non-invasive but also non-direct methods and instruments attempt to determine blood glucose content by measuring the glucose in sweat, saliva, urine or tears. These measurements, which can be quite reliable from the chemical analysis point of view, do not determine blood glucose levels because of the complicated, and not always well-defined, relation between blood glucose levels and glucose concentration in other body fluids. Other invented methods like acoustic velocity measurements in blood, are not very reliable because of the lack of well established and simple relations with blood glucose levels.